Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders

• Published in: Vaccine Vol. 36; no. 42; pp. 6282 - 6289
• Main Authors: Bartholomeus, Esther, De Neuter, Nicolas, Meysman, Pieter, Suls, Arvid, Keersmaekers, Nina, Elias, George, Jansens, Hilde, Hens, Niel, Smits, Evelien, Van Tendeloo, Viggo, Beutels, Philippe, Van Damme, Pierre, Ogunjimi, Benson, Laukens, Kris, Mortier, Geert
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 08.10.2018; Elsevier Limited
• Subjects: Adult; Antigens; Blood; Chronic infection; Current carriers; Differential gene expression; Engerix-B vaccine; Female; Gene expression; Gene Expression Profiling - methods; Gene sequencing; Genes; Granulin; Healthy Volunteers; Hepatitis; Hepatitis B; Hepatitis B - genetics; Hepatitis B - prevention & control; Hepatitis B Antibodies - immunology; Hepatitis B Vaccines - therapeutic use; Hepatitis B virus - immunology; Hepatitis B virus - pathogenicity; Humans; Immune response; Immune system; Immunization Schedule; Immunology; Infections; Kinases; Leukocytes (granulocytic); Male; Middle Aged; Morbidity; Proteins; Vaccination - methods; Vaccines; Viruses; Volunteers; Young Adult; Immune response; Differential gene expression; Engerix-B vaccine; Hepatitis B
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.09.001

As the hepatitis B virus is widely spread and responsible for considerable morbidity and mortality, WHO recommends vaccination from infancy to reduce acute infection and chronic carriers. However, current subunit vaccines are not 100% efficacious and leave 5–10% of recipients unprotected. To evaluate immune responses after Engerix-B vaccination, we determined, using mRNA-sequencing, whole blood early gene expression signatures before, at day 3 and day 7 after the first dose and correlated this with the resulting antibody titer after two vaccine doses. Our results indicate that immune related genes are differentially expressed in responders mostly at day 3 and in non-responders mostly at day 7. The most remarkable difference between responders and non-responders were the differentially expressed genes before vaccination. The granulin precursor gene (GRN) was significantly downregulated in responders while upregulated in non-responders at day 0. Furthermore, absolute granulocytes numbers were significantly higher in non-responders at day 0. The non-responders already showed an activated state of the immune system before vaccination. Furthermore, after vaccination, they exhibited a delayed and partial immune response in comparison to the responders. Our data may indicate that the baseline and untriggered immune system can influence the response upon hepatitis B vaccination.